Although many viruses are cleared by the immune system, certain retroviruses, like HIV, evade the immune system, lie dormant, spread, and cause chronic infections. The World Health Organization estimates that AIDS has killed more than 25 million people since it was first recognized. In 2007, there were 2.7 million new HIV infections and 2 million HIV-related deaths. Anti-retroviral drugs are medications for the treatment of infection by retroviruses. When several antiviral agents are taken in combination with a retroviral drug, the approach is known as highly active antiretroviral therapy (HAART). Although HAART may improve symptoms associated with infection, there is currently no cure for HIV. HAART can also have serious side-effects. Regimens can be complicated, requiring patients to take several pills at various times during the day. If patients miss a dose, drug resistance can develop. Therefore, there remains a need for improved antiviral therapies. In particular, there remains a need for antiviral therapies with reduced toxicity and improved efficacy over existing treatments.
Analogous to virus, cancer is thought to occur as a result of an immune system that is not properly removing uncontrolled proliferating cancer cells. Stimulating the immune system to recognize and eliminate cancerous cells has become a promising strategy for therapeutic treatments. For example, Provenge™ is a FDA-approved autologous cellular immunotherapy treatment. Peripheral blood leukocytes of a subject are harvested via leukapheresis. These enriched monocytes are incubated prostatic acid phosphatase (PAP) conjugated to cytokine granulocyte macrophage colony stimulating factor (PAP-GM-CSF). GM-CSF is thought to direct the target antigen to receptors on DC precursors, which then present PAP on their cell surface in a context sufficient to activate T cells for the cells that express PAP. Activated, PAP presenting DCs are administered to the subject to elicit an immune response retarding cancer growth. This strategy requires isolation and expansion of cells of the subject, and typically treatment does not entirely clear the subject of cancer or tumors. Thus, there is a need to identify improved methods.
Li et al., Clinical Immunology (2007) 123, 155-165, reported that recombinant IL-7 enhances the potency of GM-CSF-secreting tumor cell immunotherapy. Pellegrini et al., Nature Medicine, 2009, 15, 528-536, reported that when combined with a GM-CSF-secreting tumor cell immunotherapy, IL-7 prolonged the survival of tumor-bearing mice. Schroten-Loef et al., Cancer Immunol Immunother, (2009), 58:373-381, disclose a prostate cancer vaccine comprising whole cells secreting IL-7.
Williams and Park, Cancer, 1991, 67(10 Suppl):2705-7, disclose a fusion protein of the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3). See also WO 2005/0053579, WO 2005/026820, WO 2008/0014612, and U.S. Pat. Nos. 7,323,549 and 7,217,421.